Natural variation in yeast reveals multiple paths for acquiring higher stress resistance.

BACKGROUND: Organisms frequently experience environmental stresses that occur in predictable patterns and combinations. For wild Saccharomyces cerevisiae yeast growing in natural environments, cells may experience high osmotic stress when they first enter broken fruit, followed by high ethanol levels during fermentation, and then finally high levels of oxidative stress resulting from respiration of ethanol. Yeast have adapted to these patterns by evolving sophisticated "cross protection" mechanisms, where mild 'primary' doses of one stress can enhance tolerance to severe doses of a different 'secondary' stress. For example, in many yeast strains, mild osmotic or mild ethanol stresses cross protect against severe oxidative stress, which likely reflects an anticipatory response important for high fitness in nature. RESULTS: During the course of genetic mapping studies aimed at understanding the mechanisms underlying natural variation in ethanol-induced cross protection against H2O2, we found that a key H2O2 scavenging enzyme, cytosolic catalase T (Ctt1p), was absolutely essential for cross protection in a wild oak strain. This suggested the absence of other compensatory mechanisms for acquiring H2O2 resistance in that strain background under those conditions. In this study, we found surprising heterogeneity across diverse yeast strains in whether CTT1 function was fully necessary for acquired H2O2 resistance. Some strains exhibited partial dispensability of CTT1 when ethanol and/or salt were used as mild stressors, suggesting that compensatory peroxidases may play a role in acquired stress resistance in certain genetic backgrounds. We leveraged global transcriptional responses to ethanol and salt stresses in strains with different levels of CTT1 dispensability, allowing us to identify possible regulators of these alternative peroxidases and acquired stress resistance in general. CONCLUSIONS: Ultimately, this study highlights how superficially similar traits can have different underlying molecular foundations and provides a framework for understanding the diversity and regulation of stress defense mechanisms.

Longitudinal analysis of nursing home residents' T cell responses after SARS-CoV-2 mRNA vaccinations shows influence of biological sex and SARS-CoV-2 infection history.

BACKGROUND: Vaccines and vaccine boosting have blunted excess morbidity and mortality from SARS-CoV-2 infection suffered by older nursing home residents (NHR). However, the impact of repeated vaccination on the T cell response based on biological sex and prior infection of NHR remain understudied. METHODS: We examined T cell responses to mRNA vaccines to SARS-CoV-2 in a cohort of NHR and healthcare workers (HCW) over 2 years. We used IFN-γ ELIspot and flow cytometry to assess T cell response before, two weeks and 6 months after the initial series and each of two booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T cell effector function. RESULTS: We show that prior SARS-CoV-2 infection and female sex contribute to higher T cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations and suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T cell response to mRNA vaccination.

Exploring the Tl 2 H 2 potential energy surface: A comparative analysis with group 13 systems and experiment.

Thallium chemistry is experiencing unprecedented importance. Therefore, it is valuable to characterize some of the simplest thallium compounds. Stationary points along the singlet and triplet Tl 2 H 2 potential energy surface have been characterized. Stationary point geometries were optimized with the CCSD(T)/aug-cc-pwCVQZ-PP method. Harmonic vibrational frequencies were computed at the same level of theory while anharmonic vibrational frequencies were computed at the CCSD(T)/aug-cc-pwCVTZ-PP level of theory. Final energetics were obtained with the CCSDT(Q) method. Basis sets up to augmented quintuple-zeta cardinality (aug-cc-pwCV5Z-PP) were employed to obtain energetics in order to extrapolate to the complete basis set limits using the focal point approach. Zero-point vibrational energy corrections were appended to the extrapolated energies in order to determine relative energies at 0 K. It was found that the planar dibridged isomer lies lowest in energy while the linear structure lies highest in energy. The results were compared to other group 13 M 2 H 2 (M = B, Al, Ga, In, and Tl) theoretical studies and some interesting variations are found. With respect to experiment, incompatibilities exist.

The Diagnostic Utility of Cervical Spine Proprioception for Adolescent Concussion.

OBJECTIVE: Cervical spine proprioception may be impaired after concussion. Our objective was to determine the diagnostic utility of cervical spine proprioception for adolescent concussion. DESIGN: Cross-sectional. SETTING: Research laboratory. PARTICIPANTS: Adolescents ≤18 days of concussion and uninjured controls. INTERVENTIONS: N/A. MAIN OUTCOMES: Head repositioning accuracy (HRA) testing, a measure of cervical spine proprioception. The HRA test involved patients relocating their head back to a neutral starting position with eyes closed after maximal cervical spine flexion, extension, and right and left rotations. The overall HRA error score was the mean error (distance from the starting point to self-reported return to neutral) across 12 trials: 3 trials in each direction. We used t-tests to compare group means and logistic regression (outcome = group, predictor = HRA, covariates) to calculate odds ratios. We used a receiver operator characteristic curve to evaluate area under the curve (AUC) and calculate the optimal HRA cutpoint to distinguish concussion from controls. RESULTS: We enrolled and tested 46 participants with concussion (age = 15.8 ± 1.3 years, 59% female, mean = 11.3 ± 3.3 days postconcussion) and 83 uninjured controls (age = 16.1 ± 1.4 years, 88% female). The concussion group had significantly worse HRA than controls (4.3 ± 1.6 vs 2.9 ± 0.7 degrees, P < 0.001, Cohen d = 1.19). The univariable HRA model AUC was 0.81 (95% CI = 0.73, 0.90). After adjusting for age, sex, and concussion history, the multivariable model AUC improved to 0.85 (95% CI = 0.77, 0.92). The model correctly classified 80% of participants as concussion/control at a 3.5-degree cutpoint. CONCLUSIONS: Adolescents with concussion demonstrated worse cervical spine proprioception than uninjured controls. Head repositioning accuracy may offer diagnostic utility for subacute concussion.

Humoral and Cellular Immunity Induced by Adjuvanted and Standard Trivalent Influenza Vaccine in Older Nursing Home Residents.

BACKGROUND: Despite wide use of adjuvanted influenza vaccine in nursing home residents (NHR), little immunogenicity data exist for this population. METHODS: We collected blood from NHR (n = 85) living in nursing homes participating in a cluster randomized clinical trial comparing MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) with nonadjuvanted vaccine (TIV) (parent trial, NCT02882100). NHR received either vaccine during the 2016-2017 influenza season. We assessed cellular and humoral immunity using flow cytometry and hemagglutinin inhibition, antineuraminidase (enzyme-linked lectin assay), and microneutralization assays. RESULTS: Both vaccines were similarly immunogenic and induced antigen-specific antibodies and T cells, but aTIV specifically induced significantly larger 28 days after vaccination (D28) titers against A/H3N2 neuraminidase than TIV. CONCLUSIONS: NHRs respond immunologically to TIV and aTIV. From these data, the larger aTIV-induced antineuraminidase response at D28 may help explain the increased clinical protection observed in the parent clinical trial for aTIV over TIV in NHR during the A/H3N2-dominant 2016-2017 influenza season. Additionally, a decline back to prevaccination titers at 6 months after vaccination emphasizes the importance of annual vaccination against influenza. CLINICAL TRIALS REGISTRATION: NCT02882100.

Quantitative focused laser differential interferometry with hypersonic turbulent boundary layers.

The effect of turbulent wind-tunnel-wall boundary layers on density change measurements obtained with focused laser differential interferometry (FLDI) was studied using a detailed direct numerical simulation (DNS) of the wall from the Boeing/AFOSR Mach-6 Quiet Tunnel run in its noisy configuration. The DNS was probed with an FLDI model that is capable of reading in three-dimensional time-varying density fields and computing the FLDI response. Simulated FLDI measurements smooth the boundary-layer root-mean-square (RMS) profile relative to true values obtained by directly extracting the data from the DNS. The peak of the density change RMS measured by the FLDI falls within 20% of the true density change RMS. A relationship between local spatial density change and temporal density fluctuations was determined and successfully used to estimate density fluctuations from the FLDI measurements. FLDI measurements of the freestream fluctuations are found to be dominated by the off-axis tunnel-wall boundary layers for lower frequencies despite spatial suppression provided by the technique. However, low-amplitude (0.05%-5% of the mean density) target signals placed along the tunnel centerline were successfully measured over the noise of the boundary layers (which have RMS values of about 12% of the mean). Overall, FLDI was shown to be a useful technique for making quantitative turbulence measurements and to measure finite-width sinusoidal signals through turbulent boundary layers, but may not provide enough off-focus suppression to provide accurate freestream noise measurements, particularly at lower frequencies.

Performance of a novel protease-activated fluorescent imaging system for intraoperative detection of residual breast cancer during breast conserving surgery.

PURPOSE: Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20-40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types. METHODS: We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software. RESULTS: Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81-5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision. CONCLUSIONS: Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

Enhanced Recovery Minimizes Opioid Use and Hospital Stay for Patients Undergoing Mastectomy with Reconstruction.

BACKGROUND: This study examined the effects of an enhanced recovery program on inpatient opioid requirements and hospital length of stay (LOS) for mastectomy patients undergoing immediate reconstruction. METHODS: An enhanced recovery program for patients undergoing mastectomy with immediate tissue expander (TE) or implant reconstruction was evaluated by comparing a contemporary cohort of 611 patients in 2016-2018 with a historical cohort of 188 patients in 2010. Opioid use and LOS were compared over time and stratified by laterality, mastectomy type, axillary procedure, and reconstruction. Associations were assessed by uni- and multivariate analyses. RESULTS: In 2010, 95.2% of patients required intravenous (IV) opioids, with a last dose 15.5 h after completion of surgery, compared with 68.7% of patients in 2016-2018, with a last dose 1.8 h after surgery (p < 0.001). Patients prescribed gabapentin postoperatively were less likely to require inpatient IV or oral opioids (p < 0.001). The mean LOS decreased from 37 h in 2010 to 27.5 h in 2016-2018 without an increase in the readmission rate (6.9% vs. 4.1%; p = 0.112). Patients were more likely to stay more than one night if they were older (p = 0.012), had undergone bilateral mastectomies (p < 0.001) or TE reconstruction (p = 0.012), and had surgery in 2010 compared with 2016-2018 (p < 0.001). Even after adjustment for LOS, IV opioid use remained significantly associated with year of surgery (p < 0.001). CONCLUSIONS: Compared with 2010, patients undergoing mastectomy with TE or implant reconstruction in 2016-2018 required less inpatient opioids and had decreased LOS. The authors attribute this to an enhanced recovery program focused on preoperative counseling, non-opioid analgesics, and improved surgical efficiencies.

The Enigmatic P450 Decarboxylase OleT Is Capable of, but Evolved To Frustrate, Oxygen Rebound Chemistry.

OleT is a cytochrome P450 enzyme that catalyzes the removal of carbon dioxide from variable chain length fatty acids to form 1-alkenes. In this work, we examine the binding and metabolic profile of OleT with shorter chain length (n ≤ 12) fatty acids that can form liquid transportation fuels. Transient kinetics and product analyses confirm that OleT capably activates hydrogen peroxide with shorter substrates to form the high-valent intermediate Compound I and largely performs C-C bond scission. However, the enzyme also produces fatty alcohol side products using the high-valent iron oxo chemistry commonly associated with insertion of oxygen into hydrocarbons. When presented with a short chain fatty acid that can initiate the formation of Compound I, OleT oxidizes the diagnostic probe molecules norcarane and methylcyclopropane in a manner that is reminiscent of reactions of many CYP hydroxylases with radical clock substrates. These data are consistent with a decarboxylation mechanism in which Compound I abstracts a substrate hydrogen atom in the initial step. Positioning of the incipient substrate radical is a crucial element in controlling the efficiency of activated OH rebound.

A two-dimensional analysis of the sensitivity of a pulse first break to wave speed contrast on a scale below the resolution length of ray tomography.

Mapping the speed of mechanical waves traveling inside a medium is a topic of great interest across many fields from geoscience to medical diagnostics. Much work has been done to characterize the fidelity with which the geometrical features of the medium can be reconstructed and multiple resolution criteria have been proposed depending on the wave-matter interaction model used to decode the wave speed map from scattering measurements. However, these criteria do not define the accuracy with which the wave speed values can be reconstructed. Using two-dimensional simulations, it is shown that the first-arrival traveltime predicted by ray theory can be an accurate representation of the arrival of a pulse first break even in the presence of diffraction and other phenomena that are not accounted for by ray theory. As a result, ray-based tomographic inversions can yield accurate wave speed estimations also when the size of a sound speed anomaly is smaller than the resolution length of the inversion method provided that traveltimes are estimated from the signal first break. This increased sensitivity however renders the inversion more susceptible to noise since the amplitude of the signal around the first break is typically low especially when three-dimensional anomalies are considered.

American Indian Diabetes Beliefs and Practices: Anxiety, Fear, and Dread in Pregnant Women With Diabetes.

Diabetes among American Indian (AI) people is a health disparities condition that creates excessive morbidity and mortality. This research delineated culturally constructed models of type 2 diabetes among 97 pregnant women in two large AI nations in Oklahoma. The data analysis of explanatory models of type 2 diabetes revealed the participants' intense anxiety, fear, and dread related to the condition. The sample was further stratified by combinations of diabetes status: 1) absence of type 2 diabetes (n = 66), 2) type 2 diabetes prior to pregnancy (n = 4), and 3) gestational diabetes (n = 27). Patients were interviewed regarding perceptions of the etiology, course, and treatment of diabetes. The research incorporated an integrated phenomenologic and ethnographic approach using structured and semi-structured interviews to yield both quantitative and qualitative data. General findings comprised three main categories of patients' concerns regarding type 2 diabetes as an illness: 1) mechanical acts (i.e., injections), 2) medical complications, and 3) the conceptual sense of diabetes as a "severe" condition. Specific findings included significant fear and anxiety surrounding 1) the health and well-being of the unborn child, 2) the use of insulin injections, 3) blindness, 4) amputation, and 5) death. Paradoxically, although there was only a slight sense of disease severity overall, responses were punctuated with dread of specific outcomes. The latter finding is considered consistent with the presence of chronic diseases that can usually be managed but present risk of severe complications if not well controlled.

American Indian Diabetes Prevention Center: Challenges of a Health Equity Quest.

American Indians are classified by the federal government as a "health disparities population" with significant excess morbidity and mortality caused by diabetes and its many complications. The National Institute on Minority Health and Health Disparities of the National Institutes of Health has created a national program titled "Centers of Excellence" whose primary goal is the elimination of health disparities. This article describes the American Indian Diabetes Prevention Center at the University of Oklahoma Health Sciences Center, College of Public Health, in terms of its intellectual foundations rooted in a biocultural analytic model and operationalized by an interdisciplinary functioning staff. Challenges are described in terms of the monumental task of impacting health disparity conditions and in the exigencies of research collaborations with American Indian Nations located in rural areas remote to the University's health sciences urban-based hub.

Perceptions and Concerns Regarding Diabetes Mellitus During Pregnancy Among American Indian Women.

Diabetes among American Indian (AI) people is a. condition that creates excessive morbidity and mortality and is a significant health disparity. This research delineated culturally constructed models of diabetes mellitus (DM) among 97 pregnant women in 2 large AI Nations to Oklahoma. Analysis of data revealed intense anxiety, fear, and dread related to DM during pregnancy. The sample was stratified by DM status: (a) absence of DM (n = 66), (b) DM prior to pregnancy (n = 4), and (c) gestational (n = 27). Structured and semistructured interviews elicited patient culturally based explanatory models (EMs) of etiology, course, and treatment. The research incorporated an integrated phenomenologic and ethnographic approach and yielded both quantitative and qualitative data. General findings comprised the following main categories of patients' concerns regarding DM as an illness: (a) care-seeking behaviors, (b) medical management, (c) adherence and self-management, (d) complications, and (e) the conceptual sense of DM as a "severe" and feared condition. Many findings varied according to acculturation status, but all included significant fear and anxiety surrounding (a) the health and well-being of the unborn child, (b) the use of insulin injections, (c) blindness, (d) amputation, and (e) death, but with (f) a paradoxically lowered anxiety level about diabetes severity overall, while at the same time expressing extreme dread of specific outcomes. The latter finding is considered consistent with the presence of chronic conditions that can usually be managed, yet still having risk if severe.

Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation.

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of human immune cells. METHODS: We stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells. RESULTS: We found that incubation of PBMC with AS01 activated monocytes to a greater extent than any other cell population, including dendritic cells. Both classical and non-classical monocytes demonstrated this activation. RNASeq showed that TNF-ɑ and IL1R pathways were highly upregulated in response to AS01 exposure, even in older adults. CONCLUSIONS: In a PBMC co-culture, AS01 strongly activates human monocytes to upregulate costimulation markers and induce cytokines that mediate systemic inflammation. Understanding AS01's impacts on human cells opens possibilities to further address the reduced vaccine response associated with aging.

A cross-sectional analysis of reporting guideline and clinical trial registration policies in nephrology journals.

OBJECTIVE: To determine the extent to which nephrology journals recommend and require reporting guideline adherence and clinical trial registration. BACKGROUND: Despite a rising disease burden, research published on chronic kidney disease (CKD) and the field of nephrology has failed to keep pace and is limited. To improve the quality of research in the field of nephrology, reporting guidelines have been developed to minimize such deficits in research quality. However, the extent to which nephrology journals require and use reporting guidelines in addition to clinical trial registration is unknown. METHODS: Sixty-two Nephrology journals were selected through the 2021 Scopus CiteScore tool. Each journal's Instructions for Authors was assessed to determine endorsement of study design-specific reporting guidelines or clinical trial registration. Researchers used R (version 4.2.1) and RStudio to create data summaries of descriptive statistics for nephrology journal reporting guidelines. RESULTS: Clinical trial registration was required by 52% (32/62) of nephrology journals within our sample. The reporting guideline for clinical trials, CONSORT, was required by 17.74% (11/62) of journals. The EQUATOR Network was mentioned by 46.77% (29/62) of journals, while 9.67% (6/62) failed to mention the ICMJE. The reporting guideline for systematic review, PRISMA, was only required by 12.90% (8/62) of journals. When contacting journal editors, 9.67% (6/62) responded and 4.83% (3/62) provided clarifying information. CONCLUSIONS: Reporting guidelines and clinical trial registration are suboptimally required and recommended by nephrology journals. Their adoption may decrease bias and increase research quality. Thus, nephrology journals should consider a more complete endorsement of these safeguards.

Assessing Patient Risk, Benefit, and Outcomes in Drug Development: Insights From Afatinib Clinical Trials Across Diverse Cancer Indications.

PURPOSE: In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk. METHODS: In this investigation, we screened literature databases and clinical trial registries for trials of afatinib as monotherapy or in combination interventions for cancer treatment. We extracted participant demographics, adverse event characteristics, as well as clinical and surrogate endpoints for each trial. Studies were deemed positive, negative, or indeterminate based on their achieving of primary endpoints as well as their safety. RESULTS: Our search yielded 2444 articles; we excluded 2352 articles for a final inclusion of 92 trials of 8859 patients. Our sample had 49 (53%) positive trials, 27 (29%) negative trials, and 16 (17%) indeterminate trials. The most common off-label indications for afatinib were breast cancer and squamous cell carcinoma of head and neck. The median OS for all trials was 8.4 months, median PFS 3.4 months, and the total ORR was 29.6%. Our study found that trials performed in disease states beyond the initial indications were largely negative with little patient benefit. The adverse events within our trial sample appear to be in line with expectations for toxicity. IMPLICATIONS: These results are consistent with other studies that present similar findings, such as in Carlisle et al which indicate limited efficacy in nonapproved indications. Future trials should keep this potential evidence and patient burden in mind before initiation of those trials. This study contributes to the understanding of afatinib's risk-benefit profile across many clinical applications.

Effect of pH on the in vitro susceptibility of planktonic and biofilm-grown Proteus mirabilis to the quinolone antimicrobials.

AIMS: To examine the effect of elevated pH, as reported during urinary catheter infections, on quinolone activity against the urease-producing pathogen Proteus mirabilis. METHODS AND RESULTS: Susceptibility of Pr. mirabilis to nalidixic acid, norfloxacin and ciprofloxacin was examined in media of pH 5 to pH 10 by determination of MICs, MBCs, minimum biofilm eradication concentrations (MBECs) and time-kill assays. Elevation of media pH from 5 to 9 caused a 10-fold decrease in bacteriostatic activity of nalidixic acid and was also associated with loss of the characteristic 'paradoxical' bactericidal activity. Alkaline pH, however, increased both bacteriostatic and bactericidal activities of the two fluoroquinolones tested against both planktonic and biofilm-associated Pr. mirabilis; MBC and MBEC values for ciprofloxacin decreased approx. 6000-fold and 10-fold, respectively, between pH 5 and pH 9. Rates of kill of all three agents were most rapid at pH 7, the optimal pH for bacterial replication. CONCLUSIONS: pH has a pronounced effect on quinolone-mediated killing, which may be attributed to the dependence of cellular uptake on quinolone ionization state. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide rationale for the use of these agents for Pr. mirabilis eradication in alkaline environments, including urinary catheter infections: the incidence, recurrence and recalcitrance of which pose a significant burden to healthcare providers.

R3-Noria-methanesulfonate: A Molecular Cage with Superior Hyperpolarized Xenon-129 MRI Contrast.

Hyperpolarized (HP) xenon-129 (129Xe) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSO3H). This molecule is capable of two different contrast mechanisms for xenon-MRI, resulting from an increase in the effective spin-spin relaxation and hyperpolarized chemical exchange saturation transfer (HyperCEST). We have demonstrated a superior negative contrast caused by R3-Noria-MeSO3H on HP 129Xe MRI at 3.0 T as well as HyperCEST imaging of the studied macrocycle. Additionally, we have found that the complex aggregation behaviors of R3-Noria-methanesulfonate and its impact on xenon-129 relaxivity are an area for future study.

Obesity as a premature aging phenotype - implications for sarcopenic obesity.

Obesity and aging have both seen dramatic increases in prevalence throughout society. This review seeks to highlight common pathologies that present with obesity, along with the underlying risk factors, that have remarkable similarity to what is observed in the aged. These include skeletal muscle dysfunction (loss of quantity and quality), significant increases in adiposity, systemic alterations to autonomic dysfunction, reduction in nitric oxide bioavailability, increases in oxidant stress and inflammation, dysregulation of glucose homeostasis, and mitochondrial dysfunction. This review is organized by the aforementioned indices and succinctly highlights literature that demonstrates similarities between the aged and obese phenotypes in both human and animal models. As aging is an inevitability and obesity prevalence is unlikely to significantly decrease in the near future, these two phenotypes will ultimately combine as a multidimensional syndrome (a pathology termed sarcopenic obesity). Whether the pre-mature aging indices accompanying obesity are additive or synergistic upon entering aging is not yet well defined, but the goal of this review is to illustrate the potential consequences of a double aged phenotype in sarcopenic obesity. Clinically, the modifiable risk factors could be targeted specifically in obesity to allow for increased health span in the aged and sarcopenic obese populations.

Detecting feigned symptoms of depression, anxiety, and ADHD, in college students with the structured inventory of malingered symptomatology.

OBJECTIVE: Research consistently shows how easily students can feign symptoms of ADHD on self-report checklists to determine eligibility for curricular and standardized testing accommodations. However, it is unclear how easily students can feign psychological symptoms to accesses academic accommodations, making the assessment of symptom validity important in both populations. METHOD: Using a between-subjects design, 75 college students were randomly assigned to one of three groups: (1) coached feigning of ADHD, (2) coached feigning of depression and anxiety (DA), and (3) honest responding (HR). Participants completed the Depression, Anxiety, and Stress Scale (DASS-21) and the Structured Inventory of Malingered Symptomatology (SIMS). RESULTS: The SIMS showed 100% specificity, but low sensitivity (36-52%) for detecting feigned symptoms with different cutoffs. Differences on SIMS subtests were apparent by group with elevated scores for the DA group on the Affective Disorders subscale and elevation for the ADHD group on the Low Intelligence and Amnestic subscales. Participants identified as feigning by the SIMS typically reported more severe symptoms than participants not identified on the DASS-21. CONCLUSIONS: The SIMS equally classified the feigned ADHD and DA participants for both cutoff scores utilized. Potential reasons for low sensitivity rates are discussed and future research recommendations are made.